Preparation of aromatic carboxylic acids and nitro - substituted aromatic carboxylic acids



United States Patent Office 3,515,748 Patented June 2, 1970 3,515,748PREPARATION OF AROMATIC CARBOXYLIC ACIDS AND NITRO SUBSTITUTED ARO-MATIC CARBOXYLIC ACIDS Danford H. Olson and Phillip W. Storms,Littleton, Colo., assignors to Marathon Oil Company, Findlay, Ohio, acorporation of Ohio No Drawing. Filed Apr. 29, 1965, Ser. No. 452,011Int. Cl. C07c 79/46, 63/02 US. Cl. 260515 11 Claims ABSTRACT OF THEDISCLOSURE This invention relates to an improved method of preparingaromatic carboxylic acids and/or nitro-substituted aromatic carboxylicacids. In particular, the present invention relates to the preparationof benzene carboxylic acids and/or nitro-substituted benzene carboxylicacids. In its more specific and especially preferred aspects, thepresent invention relates to an improved method of preparingnitrobenzoic acids, particularly mononitrobenzoic acids such aspara-nitrobenzoic acid.

Vairous methods of preparing nitrobenzoic acids, for example, have longbeen known. Generally speaking, these prior art methods involve thesteps of first nitrating a suitable aromatic compound and then oxidizingthe nitrated compound to form the desired nitrobenzoic acid. Thus, forexample, in preparing a mononitro-substituted nitrobenzoic acid such aspara-nitrobenzoic acid in accordance with prior art practices, tolueneis first nitrated to form the corresponding nitrotoluene. Thenitrotoluene is then oxidized to obtain the desired paranitrobenzoicacid. So far as is known, no adequately satisfactory method of preparingnitrobenzoic acids, especially mononitro-substituted nitrobenzoic acidsexemplified particularly .by para-nitrobenzoic acid, heretofore has beendeveloped which avoids a multiple step procedure of the general typeoutlined above.

In accordance with the present invention, it have been discovered thatnitrobenzoic acids, especially mononitrobenzoic acids, can be preparedin substantial yields by the direct and essentially simultaneousoxidation and nitration of certain types of aromatic compounds underconditions hereafter described in detail. The reaction goes tosubstantial completion in a single step and the nitrobenzoic acid formedis thereafter recovered by conventional product separation procedures.

In achieving the objectives of this invention, a reaction mixture of thearomatic compound is formed with a nitrating agent in the presence of asulfoxide. The sulfoxide is believed to form a complex with thenitrating agent which actively participates in the oxidation-nitrationreaction. The aromatic compounds having utility in the practice of theinvention are characterized in that they have at least one substituentattached directly to the aromatic ring or nucleus which is capable, inthe described reaction mixture, of conversion to carboxyl withoutsubstantial interference with the nitration of the aromatic nucleus.

In accordance with the especially preferred aspects of the presentinvention, any benzene compound containing an activating group can beutilized. An activating group can be defined as any group which makessubstitu tion reactions proceed easier than on benzene itself anddirects substitution predominantly to ortho and para positions.Exemplary of such groups are primary and secondary alkyl groups andderivatives thereof. The derivatives of alkyl benzenes advantageouslyare of the benzylic type and may include benzene hydroperoxides.

In accordance with the particularly preferred aspects of the presentinvention, in utilizing the method of the invention to preparemononitro-substituted nitrobenzoic acids such as paranitrobenzoic acid,the aromatic compound employed should be monosubstituted and thesubstituent should be either an alkyl group, for example, or especiallydesirably, a group of the benzylic type described hereinabove.

A Wide choice of aromatic compounds is available for the purposes ofcarrying out the method of the present invention. Exemplary of aromaticcompounds having particular utility in the preparation of amononitrobenzoic acid such as para-nitrobenzoic acid are lower alkylaromatics such as toluene, phenylethane, phenylpropanes andphenylbutanes; aromatic alcohols exemplified by benzyl alcohol, phenacylalcohol, benzhydrol, and 2-phenyl-2-propanol; aromatic halides such asbenzyl chloride and benzyl bromide; aromatic hydroperoxides such asc-umene hydroperoxide and benzyl hydroperoxide; aromatic estersexemplified by benzyl acetate and benzyl formate, and the like. Thearomatic compounds utilized in preparing nitrobenzoic acids inaccordance with the practice of the present invention may containsubstituents other than the described activating group. The primaryconsiderations in the selection of such an aromatic compound for thispurpose are the susceptibility of the substituent, or substituents,thereon, other than the described activating group, to oxidation underthe conditions of the reaction, and, less importantly, steric hinderancecharacteristics of the substituent. In addition to the foregoingaromatic compounds, various lower polyalkyl substituted aromatics can beutilized to prepare a wide variety of nitro-substituted aromaticcarboxylic acids. The alkyl substituents advantageously should containfrom 1 to 5 carbon atoms and should be positioned with relation to oneanother on the aromatic nucleus to favor nitration. Xylenes areparticularly suitable for this purpose. It should be noted that, incarrying out the reaction with any of the aforementioned aromaticcompounds, the position of the substituent on the aromatic nucleus withrelation to the activating group thereon will influence the. position onthe aromatic nucleus at which the nitro group attaches.

The nitrating agent employed in the method of the present inventionshould be capable of furnishing nitronium ion and, concomitantly, ofcomplexing with the sulfoxide used in forming the reaction mixture. Ofespecial utility in this connection is dinitrogen tetroxide. Thiscompound is available commercially in various grades, but advantageouslyis used in a substantially pure form. Apart from dinitrogen tetroxide,nitric acid also can be used as the nitrating agent. The nitric acid mayvary considerably in strength. Good results can be attained with aqueoussolutions of nitric acid of strength of from about 32 to 86%, withespecially desirable results being obtained with aqueous solutionscontaining from about 50 to weight percent of nitric acid.

The proportions of aromatic compound and nitrating agent utilized in themethod of the present invention can be varied Within appreciable limitsand will, in the main, be determined by the character of the aromaticcompound and nitrating agent involved in the nitration reaction. Thus,for example, in forming a reaction mixture of toluene with dinitrogentetroxide as the nitrating agent, approximately stoichiometric ortheoretical proportions of toluene and dinitrogen tetroxide, that is, atolu cue to dinitrogen tetroxide molar ratio of about 1:3, are used.When forming a reaction mixture of toluene with nitric acid as thenitrating agent, on the other hand, a molar ratio of about 1 of tolueneto 4 of nitric acid is employed. In accordance with the preferredpractice of the invention, it has been found advantageous to employ aslight excess, of the order of 5 to over stoichiometric or theoreticalproportions, of the nitrating agent.

As indicated hereinabove, the objectives of the present invention areattained by carrying out the reaction between the aromatic compound andthe nitrating agent in the presence of a sulfoxide of the type having aformula corresponding to wherein Rand R are the same or difi'ere'nt, andmay be alkyl or aryl. Dimethylsulfoxide is especially useful for thispurpose. Other sulfoxides that can be used are diethylsulfoxide,methylsulfinylethane, methylsulfinylpropane, methylsulfinylbutane,diphenylsulfoxide, phenylsulfinylethane, and the like, and compatiblemixtures of the same.

Apart from its function of reacting with the nitrating agent to form acomplex which acts as a carrier for the nitronium ion furnished by thenitrating agent thereby to facilitate nitration of the aromaticcompound, the sulfoxide advantageously also is used in the method ofthis invention to provide a medium for carrying out theoxidation-nitration reaction. More specifically, in this latterconnection, due to the exothermic character of the reaction, the volumeof the sulfoxide utilized can be regulated in a manner to enable thereaction mixture to be maintained within a temperature range mostfavorable to the formation of the nitrobenzoic acid. In accordance withthe preferred practice of this invention, preparation of the reactionmixture is initiated by first introducing the aromatic compound into thesulfoxide. Similarly, particularly when dinitrogen tetroxide is used,the nitrating agent is separately incorporated into a suitable volume ofthe sulfoxide. The temperature of the reaction mixture advantageouslycan then be controlled by adding the sulfoxide solution of the nitratingagent to the aromatic compound solution gradually or in increments.

The temperature at which the method of the present invention is carriedout may range from about 40 degrees C. to about 100 degrees C., moreadvantageously from degrees C. to 80 degrees C., with about 75 degreesC. being especially preferred. While not required, temperature controlequipment can be utilized to assure control of the temperature of thereaction mixture within the ranges indicated.

'While the method of the present invention has been described withreference to its particular utility in the preparation of nitro-substituted aromatic compounds, especially nitro-substituted benzene compounds,the method also can be used to advantage in the preparation of aromaticcarboxylic acids. In accordance with this aspect of the invention, anybenzene compound containing a deactivating group can be defined as anygroup which, under the conditions of the described reaction, isconverted to a carboxyl group and does not influence nitration on thebenzene ring. Exemplary of compounds containing such a deactivatinggroup are aromatic ketones exemplified by acetophenone,ethylphenylketone, and benzophenone; aromatic aldehydes such asbenzaldehyde and m-tolualdehyde; aromatic esters exemplified bymethylbenzoate and ethylbenzoate; and aromatic amides such as benzamide.In carrying out the reaction of this invention with an aromatic compoundcontaining both an activating group and a deactivating group as definedhereinabove, the nature of the product, or products, ob

tained would be determined by the group which had the greatest elfect.

In order that the full details of the present invention will be evenbetter understood, the following examples are provided. These examplesare illustrative of the practice of the method of the invention and itshould be understood that variations may be made therein in a number ofparticulars without in any way departing from the fundamental principlesand teachings provided herein. The examples, therefore, are not to beconstrued in any way as limitative of the scope of the invention.

Example 1 Example 2 To a solution of 0.1 gram-mole of cumene hydrotperoxide in 150 ml. of dimethylsulfoxide is addeda solution of 0.163gram mole of dinitrogen tetroxide .in 50 ml. of dimethylsulfoxide. Theaddition rate is regulated to maintain the reaction temperature at 50degrees, C. The; reaction mixture is stirred for one hour and thedimethyli sulfoxide is then removed by distillation in vacuo. A solidproduct weighing 14.7 grams is obtained. The solid product is dissolvedin 25 ml. of a 10 percent sodium hydroxide solution and washed withether. Acidification of the caustic solution yields a solid which ispurified by sublimation. The pure product is identified aspara-nitrobenzoic acid.

Example 3 To a solution of 0.1 gram mole of cumene hydroperoxide in 150ml. of methylsulfinylethane at 20 degrees C. is added slowly a solutionof 0.16 gram mole of dinitrogen tetroxide in 50 ml. ofmethylsulfinylethane. The temperature of the reaction rises to 5060degrees C. where it is maintained by controlled rate of addition of thedinitrogen tetroxide solution. After addition of the dinitrogentetroxide solution is completed, the solution is stirred for one hour.The methylsulfinylethane and excess.

dinitrogen tetroxide are evaporated in vacuo leaving 15.1 grams of asolid product which is base-soluble. The product is identified aspara-nitrobenzoic acid by its infrared spectrum compared to that of anauthentic sample;

yield 88.3%.

Example 4 To a solution of 0.1 gram mole of cumene hydroperoxide in 150ml. of dimethylsulfoxide, 15 grams (0.16 gram mole) of 70% nitric acidin 25 ml. of dimethylsulfoxide is added dropwise. The temperature of thereaction mixture rises to degrees C. and is maintained at thattemperature until all of the nitric acid solution is added. The mixtureis stirred for 30 minutes and isathen evaporated in vacuo. The resultingsolid product is dissolved in 20 ml. of a 10 percent solution of sodiumhydroxide and washed with ether. Acidification of the canstic solutionyields a solid which is purified by sublimation. The pure product isidentified as para-nitrobenzoic acid.

Example 5 A stream of dinitrogen tetroxide is passed into a solution of25 g. of m-xylene in 150 ml. of dimethylsulfoxide at degrees C. for 2hours. The excess dinitrogen tetroxide is removed with a stream ofnitrogen and the solution is poured into 200 ml. of water and made basicwith sodium carbonate. The solution is extracted with methylene chlorideand the aqueous solution is evaporated to dry salts. The salts areacidified With concentrated hydrochloric acid and again evaporated todryness. The dry acid salts are washed with isopropyl alcohol. Thealcohol solution is evaporated to dryness giving a yellow solid. Thesolid is dissolved in aqueous sodium carbonate and the solution isacidified with hydrochloric acid. A yellow precipitate is slowly formedwhich is filtered and dried. Infrared and nuclear magnetic resonancespectra show the yellow solid to be m-toluic acid containing 4-nitro and6-nitro-m-toluic acids.

Example 6 To a solution of 0.1 gram-mole of meta-tolualdehyde in 150 ml.of dimethylsulfoxide is added 0.16 gram-mole of dinitrogen tetroxide in100 ml. of dimethylsulfoxide. The procedure outlined in Example 2 isfollowed. The product obtained is identified as m-toluic acid.

Example 7 To a solution of 0.1 gram-mole of 2 methylacetophenone in 150ml. of dimethylsulfoxide is added a solution of 0.15 gram-mole ofdinitrogen tetroxide in 50 ml. of dimethylsulfoxide. The procedureoutlined in Example 2 is followed. The product obtained is identified asotoluic acid.

While the invention has been described in detail, it should beunderstood that various modifications may be made in the light of theteachings hereof without departing from the spirit and scope of theinvention.

What is claimed is:

1. A method of preparing nitrobenzoic acid comprising forming a reactionmixture consisting essentially of a substituted benzene compound, anitrating agent selected from the group consisting of dinitrogentetroxide and nitric acid, and a di-lower alkyl sulfoxide solvent, thebenzene compound having at least one substituent on the benzene nucleus,said at least one substituent being characterized in that it contains abenzylic carbon atom with at least one hydrogen or oxygen attacheddirectly to the benzylic carbon atom, allowing the reaction to proceedat a temperature of from about 40 C. to about 100 C., and recovering thenitrobenzoic acid formed.

2. A method of preparing nitrobenzoic acids comprising forming areaction mixture consisting essentially of a substituted benzenecompound, a nitrating agent selected from the group consisting ofdinitrogen tetroxide and nitric acid, and a di-lower alkyl sulfoxidesolvent, the benzene compound having at least one substituent of thebenzylic type, allowing the reaction to proceed at a temperature of fromabout 40 C. to about 100 C., and recovering the nitrobenzoic acidformed.

3. A method of preparing benzene carboxylic acids comprising forming areaction mixture consisting essentially of a substituted "benzenecompound and the reaction product of a nitrating agent selected from thegroup consisting of dinitrogen tetroxide and nitric acid, and a di-loweralkyl sulfoxide solvent, the benzene compound having at least onesubstituent attached directly to the aromatic nucleus, said at least onesubstituent being characterized in that it contains a benzylic carbonatom with at least one hydrogen or oxygen attached directly to thebenzylic carbon atom, allowing the reaction to proceed at a temperaturein the range of from about 40 C. to about 100 C., and recovering thebenzene carboxylic acid formed.

4. A method of preparing nitrobenzoic acids comprising forming areaction mixture consisting essentially of a substituted benzenecompound and the reaction product of a di-lower alkyl sulfoxide solventand a nitrating agent selected from the group consisting of dinitrogentetroxide and nitric acid, the benzene compound having at least onesubstituent attached directly to the aromatic nucleus, said at least onesubstituent being characterized in that it contains a benzylic carbonatom with a least one hydrogen or oxygen attached directly to thebenzylic carbon atom, allowing the reaction to proceed at a temperatureof from about 40 degrees to 100 degrees C., and recovering thenitrobenzoic acid formed.

5. A method of preparing para-nitrobenzoic acid comprising forming areaction mixture consisting essentially of a mono-substitutedmononucleated benzene compound and a reaction product of a nitratingagent selected from the group consisting of dinitrogen tetroxide andnitric acid, and a di-lower alkyl sulfoxide solvent, the substituent onthe benzene compound being characterized in that it contains a benzyliccarbon atom with at least one hydrogen or oxygen attached directly tothe benzylic carbon atom, allowing the reaction to go to substantialcompletion at a temperature of from about 40 C. to about 100 C., andrecovering the para-nitrobenzoic acid formed.

6. A method of preparing para-nitrobenzoic acid comprising forming areaction mixture consisting essentially of a mono-substitutedmononucleated benzene compound, dinitrogen tetroxide anddimethylsulfoxide, the substituent on the benzene compound beingcharacterized in that it contains a benzylic carbon atom with at leastone hydrogen or oxygen attached directly to the benzylic carbon atom,allowing the reaction to proceed at a temperature of from about 40 C. toabout 100 C., and recovering the para-nitrobenzoic acid formed.

7. A method of preparing para-nitrobenzoic acid comprising a reactionmixture consisting essentially of cumene hydroperoxide, a nitratingagent selected from the group consisting of dinitrogen tetroxide andnitric acid, and a di-lower alkyl sulfoxide solvent, allowing thereaction to proceed at a temperature of from about 40 C. to about 100C., and recovering the para-nitrobenzoic acid formed.

8. A method of preparing para-nitrobenzoic acid comprising forrning areaction mixture consisting essentially of toluene, a nitrating agentselected from the group consisting of dinitrogen tetroxide and nitricacid, and a dilower alkyl sulfoxide solvent, allowing the reaction toproceed at a temperature of from about 40 C. to about 100 C., andrecovering the para-nitrobenzoic acid formed.

9. A method of preparing nitrobenzoic acid comprising forming a reactionmixture consisting essentially of xylene, dinitrogen tetroxide anddimethylsulfoxide, allowing the reaction to proceed at a temperature offrom about 40 C. to about 100 C., and recovering the nitrobenzoic acidformed.

10. A method of preparing para-nitrobenzoic acid comprising forming areaction mixture of cumene hydroperoxide and dinitrogen tetroxide in thepresence of dimethylsulfoxide, maintaining the reaction at a temperatureof from about 40 degrees C. to 100 degrees C. until the reaction hasgone to substantial completion, and recovering the para-nitrobenzoicacid formed.

11. A method of preparing para-nitrobenzoic acid comprising forming areaction mixture of cumene hydroperoxide and dinitrogen tetroxide in thepresence of dimethylsulfoxide, allowing the reaction to proceed at atemperature of about degrees C., and recovering the paranitrobenzoicacid formed.

References Cited UNITED STATES PATENTS 9/ 1966 Bartholome et a1 260524OTHER REFERENCES JAMES A. PATTEN, Primary Examiner U .8. Cl. X.R.260-524 Patent NO. 3, 515,148 Dated June 2, 1970 Danford H. Olson andPhillip W. Storms Inventor(s) It is certified that error appears in theabove-identified patent and LhaL said Letters Patent are herebycorrected as shown below:

Col. 1, line 16: "aromaic should read -aromatic Col. 1, line 52: "have'should read -has-- Col', 3, line 64: should read -ing a "deactivatinggroup" can be utilized. A "deactivating group" may be defined as anygroup Signed and sealed this 18th day of January 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GQTTSCHALK Attesting Officer ActingCommissioner of Patents

